Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: no glp, only similar to guideline
Data waiving:
other justification
Justification for data waiving:
other:
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 and 13 weeks
Frequency of treatment:
daily with diet
Remarks:
Doses / Concentrations:
0.00, 0.03, 0.10, 0.30, 1.00 % Sn in diet
Basis:
nominal in diet
No. of animals per sex per dose:
10 animals per sex per dose per timeframe.
Control animals:
yes
Dose descriptor:
NOEL
Effect level:
> 22 - < 33 other: mg Sn /kg bw day
Based on:
element
Sex:
male/female
Critical effects observed:
not specified
Conclusions:
Severe growth retardation,
decreased food efficiency, slight anaemia and slight histological changes in the liver were
observed with 0.3 70 or more of stannous sulphate.

As NOAL a value of 22-33 mg Sn/kg bw day was determined, no LOAEL was fouind.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
52.9 ng/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
201/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study, glp
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Deviations:
not applicable
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
other: RccHanTM:WIST rats
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: 2.7 - 3.0 µm
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 weeks (6 hours per day, 5 days per week)
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0 µg/L
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
2.44 µg/L
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
9.19 µg/L
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
87.9 µg/L
Basis:
analytical conc.
No. of animals per sex per dose:
10
Control animals:
yes
Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
9.91 other: µg/L
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LOAEC
Remarks:
local
Effect level:
2.44 other: µg/L
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: findings were restricted to the lungs and tracheobronchial lymph nodes.
Critical effects observed:
not specified

Summary data are presented below:

Group Exposure level (μg/L) Particle size

Target Achieved MMAD (μm) sg

2 2.3 2.44 3.0 2.54

3 9.1 9.19 3.0 2.41

4 80 87.9 2.7 2.44

MMAD Mass median aerodynamic diameter

sg Geometric standard deviation

The achieved levels were 106, 101 and 110% of the target concentrations for Groups 2, 3 and

4 respectively. The Mass Median Aerodynamic Diameters for Groups 2, 3 and 4 are within

the ideal range (1-3 μm) for a repeat dose inhalation study.

There were no treatment related clinical signs observed during the detailed weekly physical

examination.

Lower body weight gain was evident for males exposed to 9.19 μg/L and 87.9 μg/L and for

all females exposed to tin monoxide. Food consumption was also slightly reduced for males

exposed to 87.9 μg/L.

A statistically significant increase in group mean activated partial thromboplastin times were

evident for males exposed to 9.19 and 87.9 μg/L and all females exposed to tin monoxide.

Group mean venous blood oxygen saturation levels were increased for females exposed to

9.19 μg/L and both sexes exposed to 87.9 μg/L.

Two hours after the completion of exposure in Week 4, tin was detected in the plasma of a

single male and female exposed to 9.19 μg/L and in all animals exposed to 87.9 μg/L. Tin

was not quantifiable in control animals or animals exposed to 2.44 μg/L.

Group mean lung and bronchi weights (adjusted for terminal body weight) were greater than

control for all animals exposed to tin monoxide.

Histopathological changes related to treatment were observed within the lungs (the

accumulation of pigmented and flocculent material within alveoli, variably accompanied by

both diffuse and local aggregations of alveolar macrophages, and increased cellularity of the

BALT), tracheobronchial and mediastinal lymph nodes (increased general cellularity, with or

without the accumulation of pigmented material), larynx (pigment accumulation within the

epithelium and lamina propria) and kidneys (increased tubular pigment). Observations within

the larynx and lungs were considered to reflect the accumulation of inhaled test article, with

attempted clearance by the local mononuclear-phagocyte system. Accompanying findings

within the local lymph nodes and kidneys were considered to represent the subsequent

systemic dissemination of test article. Findings were more pronounced, in terms of incidence

and severity, amongst animals dosed with 87.9 μg/L, and displayed a clear dose-related

response. Amongst animals dosed with 2.44 μg/L, findings were restricted to the lungs and

tracheobronchial lymph nodes

Conclusions:
NOAEC (systemic) 9.19 µg/LK
LOAEC (local) 2.44 µg/L (findings were restricted to the lungs and
tracheobronchial lymph nodes)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
9.19 ng/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
201/2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study, glp
Qualifier:
according to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Deviations:
not applicable
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
other: RccHanTM:WIST rats
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: 2.7 - 3.0 µm
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 weeks (6 hours per day, 5 days per week)
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0 µg/L
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
2.44 µg/L
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
9.19 µg/L
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
87.9 µg/L
Basis:
analytical conc.
No. of animals per sex per dose:
10
Control animals:
yes
Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
9.91 other: µg/L
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LOAEC
Remarks:
local
Effect level:
2.44 other: µg/L
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: findings were restricted to the lungs and tracheobronchial lymph nodes.
Critical effects observed:
not specified

Summary data are presented below:

Group Exposure level (μg/L) Particle size

Target Achieved MMAD (μm) sg

2 2.3 2.44 3.0 2.54

3 9.1 9.19 3.0 2.41

4 80 87.9 2.7 2.44

MMAD Mass median aerodynamic diameter

sg Geometric standard deviation

The achieved levels were 106, 101 and 110% of the target concentrations for Groups 2, 3 and

4 respectively. The Mass Median Aerodynamic Diameters for Groups 2, 3 and 4 are within

the ideal range (1-3 μm) for a repeat dose inhalation study.

There were no treatment related clinical signs observed during the detailed weekly physical

examination.

Lower body weight gain was evident for males exposed to 9.19 μg/L and 87.9 μg/L and for

all females exposed to tin monoxide. Food consumption was also slightly reduced for males

exposed to 87.9 μg/L.

A statistically significant increase in group mean activated partial thromboplastin times were

evident for males exposed to 9.19 and 87.9 μg/L and all females exposed to tin monoxide.

Group mean venous blood oxygen saturation levels were increased for females exposed to

9.19 μg/L and both sexes exposed to 87.9 μg/L.

Two hours after the completion of exposure in Week 4, tin was detected in the plasma of a

single male and female exposed to 9.19 μg/L and in all animals exposed to 87.9 μg/L. Tin

was not quantifiable in control animals or animals exposed to 2.44 μg/L.

Group mean lung and bronchi weights (adjusted for terminal body weight) were greater than

control for all animals exposed to tin monoxide.

Histopathological changes related to treatment were observed within the lungs (the

accumulation of pigmented and flocculent material within alveoli, variably accompanied by

both diffuse and local aggregations of alveolar macrophages, and increased cellularity of the

BALT), tracheobronchial and mediastinal lymph nodes (increased general cellularity, with or

without the accumulation of pigmented material), larynx (pigment accumulation within the

epithelium and lamina propria) and kidneys (increased tubular pigment). Observations within

the larynx and lungs were considered to reflect the accumulation of inhaled test article, with

attempted clearance by the local mononuclear-phagocyte system. Accompanying findings

within the local lymph nodes and kidneys were considered to represent the subsequent

systemic dissemination of test article. Findings were more pronounced, in terms of incidence

and severity, amongst animals dosed with 87.9 μg/L, and displayed a clear dose-related

response. Amongst animals dosed with 2.44 μg/L, findings were restricted to the lungs and

tracheobronchial lymph nodes

Conclusions:
NOAEC (systemic) 9.19 µg/LK
LOAEC (local) 2.44 µg/L (findings were restricted to the lungs and
tracheobronchial lymph nodes)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEC
2.44 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
SnO reachts in stomach with HCL to SnCl_2, no new study performed in due to animal protection.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Due to the low incidence and severity of findings for animals exposed to 9.19 μg/L, they
were considered to be non-adverse

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Amongst animals dosed with 2.44 μg/L, findings were restricted to the lungs and
tracheobronchial lymph nodes

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: larynx; respiratory: trachea; urogenital: kidneys

Justification for classification or non-classification

Under consideration of Regulation (EC) 1272/2008 Annex 1 Section 3.9.2 and the outcome of above named OECD 412 study (NOAEL 9.19 µg SnO /L) it is required to classify the substance as STOT RE1 – H372.